Preventive Use of Tamoxifen Is Allowed

By ROBERT PEAR

Published: October 30, 1998

WASHINGTON, Oct. 29—
The Government approved use of the drug tamoxifen today to help prevent or delay the development of breast cancer in healthy women who have a very high risk of getting the disease.

The manufacturer, Zeneca Pharmaceuticals, said it would distribute computer disks, developed with the National Cancer Institute, to doctors to help them assign precise scores on a risk table to individual women. The scores would then be used to help a doctor and patient decide whether the drug should be prescribed.

Zeneca said it would immediately start promoting the drug among doctors and then conduct a large advertising campaign intended for women early next year. The company said it would run advertisements in widely circulated magazines and newspapers and might run commercials on television and radio as well.

The computer disk includes questions to assess a woman's risk of developing breast cancer. Older women, women with a family history of breast cancer, women who had a first menstrual period before the age of 12 and women who first became pregnant after 30 are at increased risk, researchers say.

For women with one or more of these factors, doctors may conclude that the benefits of tamoxifen outweigh the possible side effects, which include blood clots in the lungs or major veins and cancer of the lining of the uterus, officials said.

The medication has been used for more than 20 years to treat breast cancer. But today the Food and Drug Administration approved a new use, to reduce the incidence of breast cancer. Federal officials said it was apparently the first anticancer drug to be approved for people who do not have the disease.

Studies by the National Cancer Institute found that for women at high risk of getting breast cancer tamoxifen reduced the chances of getting it by 44 percent, though it does not eliminate the risk, and the long-term effects of taking the drug are inknown.

Dr. Michael A. Friedman, the Acting Commissioner of Food and Drugs, said, ''F.D.A. strongly advises women and their doctors to carefully weigh the benefits and risks of tamoxifen before patients use the drug.''

Zeneca declined to estimate the size of the prospective new market for tamoxifen. But Mary Lynn Carver, a spokeswoman for the company, said that 29 million women were at increased risk for breast cancer and ''should discuss their risk with their doctors and determine if tamoxifen therapy is appropriate.''

The drug costs $80 to $100 a month, Ms. Carver said. The recommended course of therapy lasts five years, but the protective effects appear to last five years after a woman stops taking the drug, she added.

Zeneca sells tamoxifen under the name Nolvadex. The company, based in Wilmington, Del., is a subsidiary of Zeneca Group P.L.C., an $8.6 billion bioscience company based in London.

A business analyst who follows the pharmaceutical industry estimated that sales would increase 20 percent to 30 percent. ''The safety profile is not pefect for a product that would be used on a large patient base or for a long time,'' said the analyst, Sergio Traversa, of Mehta Partners.

Ms. Carver, the Zeneca spokeswoman, said sales of tamoxifen in the United States totaled $320 million last year.

Traversa noted that Eli Lilly & Company is also aiming at the breast-cancer prevention market, and is studying the anticancer properties of its drug Evista, which seems to have fewer side effects.

The computer disk Zeneca will distribute to doctors calculates a score for each patient, based on the woman's answers to various questions. Zeneca says a woman with a score of 1.67 or greater should talk to her doctor about her breast-cancer risk and the use of tamoxifen.

Ms. Carver gave these examples of how the risk-assessment system works:

*A 45-year-old woman, had her first menstrual period at the age of 12 and her first child at 38. Her mother died of breast cancer, and her sister is being treated for the disease. The woman has a risk score of 2.4 and should therefore consider taking the drug.

*A 40-year-old white woman, had her first menstrual period at the age of 12 and has not had any children. Her mother and sister have had breast cancer, and a breast biopsy found that the woman had abnormal noncancerous cells. The woman has a risk score of 5.9 and should therefore discuss the possibility of taking tamoxifen with her doctor.

*A 35-year-old black woman, was 15 when she had her first menstrual period and was 20 when she had her first child. No close relatives have had breast cancer. She herself has had two breast biopsies that found abnormal noncancerous cells. Her score is 1.1, so she is not a candidate to use the drug.

Cynthia A. Pearson, executive director of the National Women's Health Network, a women's health advocacy group, said healthy women should be cautious about using the drug approved today. ''This is a premature approval,'' she asserted. ''There's no way to know yet whether tamoxifen can truly prevent breast cancer or merely delay it.''

In addition, Ms. Pearson said she worried that heavy advertising could lead to overuse of the drug. Women, she said, may underestimate the danger of ''serious, even fatal, complications.''

Scientists do not know exactly how tamoxifen works, but they have a theory of one possible mechanism. Estrogen, a hormone, is believed to stimulate the growth of cancer cells, and tamoxifen is believed to block the action of natural estrogens in breast tissue, thus inhibiting the growth of breast-cancer cells.

Federal officials and Zeneca executives sounded a similar note in describing the significance of today's decision.

Donna E. Shalala, the Secretary of Health and Human Services, said, ''Today's action provides an important new option for some women at heightened risk of breast cancer,'' the second leading cause of cancer death among American women.

Robert C. Black, the president of Zeneca Pharmaceuticals, said: ''For the millions of women who are at high risk of developing breast cancer, there is now something they can do to reduce the risk of developing the disease.''

Clinical trials of tamoxifen were halted 14 months early, in March of this year, after scientists found that the drug sharply reduced the incidence of breast cancer.

Dr. Friedman of the F.D.A. said the risk of uterine cancer for women taking tamoxifen was about three times the risk for women in the general population not taking it. Zeneca said such cancer occurred in 20 to 30 women among every 10,000 treated with tamoxifen in a year. By contrast, it said, current data indicate that there are 7 cases of such cancer each year for every 10,000 healthy women in the general population.

The large-scale test of tamoxifen involved 13,388 women at high risk of breast cancer. Half took the drug and 85 of them developed breast cancer; half took a placebo and 154 of them developed breast cancer.